title: P50 sensory gating and smoking in the general population.
abstract: P50 gating is a major functional biomarker in research on schizophrenia and other psychiatric conditions with high smoking prevalence. It is used as endophenotype for studying nicotinic systems genetics and as surrogate endpoint measure for drug development of nicotinic agonists. Surprisingly, little is known about P50 gating in the general population and the relationship to smoking-related characteristics. In this multicenter study at six academic institutions throughout Germany, n=907 never-smokers (NS<20 cigarettes/lifetime), n=463 light smokers (LS) with Fagerström Test for Nicotine Dependence (FTND)≥4 and n=353 heavy smokers (HS, FTND<4) were randomly selected from the general population. As part of a standardized protocol for investigating the genetics of nicotine dependence (ND), an auditory P50 paradigm was applied. The main outcome measure was P50-amplitude difference followed by time-frequency analyses and functional imaging (sLORETA). Reduced P50 gating was found in HS compared to NS with LS taking an intermediate position-correlating with the degree of ND. sLORETA and time-frequency analyses indicate that high-frequency oscillations in frontal brain regions are particularly affected. With growing age, P50 gating increased in (heavy) smokers. This is the first large-scale study (normative sample data) on P50 sensory gating and smoking in the general population. Diminished gating of P50 and associated high-frequency oscillations in the frontal brain region are indications of a deficient inhibitory cortical function in nicotine-dependent smokers. The suitability and application of sensory P50 gating as functional biomarker with regard to genetic and pharmacological studies is discussed.
authors.affiliation: Department of Psychiatry, Heinrich-Heine University Düsseldorf, Bergische Landstrasse 2, Düsseldorf, Germany. juergen.brinkmeyer@lvr.de
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brinkmeyer
authors.forename: Arian
authors.initials: A
authors.lastname: Mobascher
authors.forename: Francesco
authors.initials: F
authors.lastname: Musso
authors.forename: Melanie
authors.initials: M
authors.lastname: Schmitz
authors.forename: Michael
authors.initials: M
authors.lastname: Wagner
authors.forename: Ingo
authors.initials: I
authors.lastname: Frommann
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.forename: Katja N
authors.initials: KN
authors.lastname: Spreckelmeyer
authors.forename: Thomas
authors.initials: T
authors.lastname: Wienker
authors.forename: Amalia
authors.initials: A
authors.lastname: Díaz-Lacava
authors.forename: Daniela
authors.initials: D
authors.lastname: Holler
authors.forename: Norbert
authors.initials: N
authors.lastname: Dahmen
authors.forename: Norbert
authors.initials: N
authors.lastname: Thuerauf
authors.forename: Marion
authors.initials: M
authors.lastname: Clepce
authors.forename: Falk
authors.initials: F
authors.lastname: Kiefer
authors.forename: Walter
authors.initials: W
authors.lastname: de Millas
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
authors.forename: Georg
authors.initials: G
authors.lastname: Winterer
mesh_terms: D000293:Adolescent; D000328:Adult; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000503:physiopathology*; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory / Q000235:genetics* / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D055139:Sensory Gating / Q000502:physiology*; D012815:Signal Processing, Computer-Assisted; D012907:Smoking / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D055815:Young Adult